Main article: 2010 FIFA World Cup knockout stageAll times listed are South African Standard Time (UTC+02)The knockout stage comprised the 16 teams that advanced from the group stage of the tournament. There were four rounds of matches, with each round eliminating half of the teams entering that round. The successive rounds were the round of 16, quarter-finals, semi-finals, and the final. There was also a play-off to decide third and fourth place. For each game in the knockout stage, any draw at 90 minutes was followed by thirty minutes of extra time; if scores were still level, there was a penalty shootout to determine who progressed to the next round.[69]

In this round, each group winner (A-H) was paired against the runner-up from another group.South American teams again performed strongly in the round of 16, with four teams advancing to the quarter-finals including Brazil who defeated fellow South Americans Chile.England's 4–1 loss to Germany was their biggest ever margin of defeat at a World Cup finals.[70][71] It was also the first time that a World Cup finals match between these two traditional rivals had a decisive result in regulation time, their three previous meetings all being tied at 90 minutes, with two settled in extra time and one in a penalty shootout.Ghana defeated the United States to become the third African team to reach the last eight (after Cameroon in 1990 and Senegal in 2002), and the only African team to have achieved both a top 8 finish and a separate top 16 finish (in 2006).Paraguay and Ghana reached the quarter-finals for the first time.The round was marked by some controversial referees' decisions, including:A disallowed goal by England in their 4–1 loss against Germany, where the shot by Frank Lampard was seen to cross the goal line when shown on television broadcast replays.An allowed goal by Argentina in their 3–1 win over Mexico, where Argentine striker Carlos Tevez was seen to be offside when shown on television broadcast replays, which were shown inside the stadium shortly after the incident.FIFA President Sepp Blatter took the unusual step of apologising to England and Mexico for the decisions that went against them, saying: "Yesterday I spoke to the two federations directly concerned by referees' mistakes [...] I apologised to England and Mexico. The English said thank you and accepted that you can win some and you lose some and the Mexicans bowed their head and accepted it."[72] Blatter also promised to re-open the discussion regarding devices which monitor possible goals and make that information immediately available to match officials, saying: "We will naturally take on board the discussion on technology and have the first opportunity in July at the business meeting."[72] Blatter's call came less than four months after FIFA general secretary Jérôme Valcke said the door was closed on goal-line technology and video replays after a vote by the IFAB.[72]

The three quarter-finals between European and South American teams all resulted in wins for Europeans. Germany had a 4–0 victory over Argentina, and the Netherlands came from behind to beat Brazil 2–1, handing the Brazilians their first loss in a World Cup match held outside Europe (other than in a penalty shootout) since 1950 when Uruguay won the decisive match 2–1.[73] Spain reached the final four for the first time since 1950 after a 1–0 win over Paraguay. Uruguay, the only South American team to reach the semi-finals, overcame Ghana in a penalty shoot-out after a 1–1 draw in which Ghana missed a penalty at the end of extra time after Luis Suárez controversially handled the ball on the line.

The Netherlands qualified for the final for the third time with a 3–2 win over Uruguay. Spain reached their first ever final with a 1–0 victory over Germany. As a result, it was the first World Cup final not to feature at least one of Brazil, Italy, Germany or Argentina.

Main article: 2010 FIFA World Cup FinalThe final was held on 11 July 2010 at Soccer City, Johannesburg. Spain defeated the Netherlands 1–0, with an extra time goal from Andrés Iniesta. Iniesta scored the latest winning goal in a FIFA World Cup final (116').[75] The win gave Spain their first World Cup title, becoming the eighth team to win it. This made them the first new winner without home advantage since Brazil in 1958,[76] and the first team to win the tournament after having lost their opening game.[61]A large number of fouls were committed in the final match. Referee Howard Webb handed out 14 yellow cards, more than doubling the previous record for this fixture, set when Argentina and West Germany shared six cards in 1986,[61] and John Heitinga of the Netherlands was sent off for receiving a second yellow card. The Netherlands had chances to score, most notably in the 60th minute when Arjen Robben was released by Wesley Sneijder to be one-on-one with Spain's goalkeeper Iker Casillas, only for Casillas to save the shot with an outstretched leg. For Spain, Sergio Ramos missed a free header from a corner kick when he was unmarked.[77] Iniesta finally broke the deadlock in extra time, scoring a volleyed shot from a pass by Cesc Fàbregas.[78]This result marked the first time that two different teams from the same continent had won successive World Cups (following Italy in 2006), and saw Europe reaching 10 World Cup titles, surpassing South America's nine titles. Spain became the first team since West Germany in 1974 to win the World Cup as European champions. The result also marked the first time that a European nation had won a World Cup Finals that was not hosted on European soil.A closing ceremony was held before the final, featuring singer Shakira. Afterwards, the former South African President Nelson Mandela made a brief appearance on the pitch, wheeled in by a motorcart.[65][79]